title: Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study.
abstract: A growing body of literature finds gender differences in ADHD. However, little is known about the causes of these differences. One possibility is that ADHD risk genes have sexually dimorphic effects. We have investigated four ADHD candidate genes (COMT, SLC6A2, MAOA, SLC6A4) for which there is evidence of sexually dimorphic effects. Past neurobiological and genetic studies suggest that COMT, and SLC6A4 variants may have a greater influence on males and that SLC6A2, and MAOA variants may have a greater influence on females. Our results indicate that genetic associations are stronger when stratified by sex and in the same direction as the previous neurobiological studies indicate: associations were stronger in males for COMT, SLC6A4 and stronger in females for SLC6A2, MAOA. Moreover, we found a statistically significant gender effect in the case of COMT (P = 0.007) when we pooled our work with a prior study. In conclusion, we have found some evidence suggesting that the genetic association for these genes with ADHD may be influenced by the sex of the affected individual. Although our results are not fully validated yet, they should motivate further investigation of gender effects in ADHD genetic association studies.
authors.affiliation: Pediatric Psychopharmacology Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. jbiederman@partners.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.forename: Jang Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Alysa E
authors.initials: AE
authors.lastname: Doyle
authors.forename: Eric
authors.initials: E
authors.lastname: Mick
authors.forename: Jesen
authors.initials: J
authors.lastname: Fagerness
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007407:Interviews as Topic; D015810:Linkage Disequilibrium; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D035781:Siblings; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase